The proposed research program involves researchers and administrative staff from four institutions: the University of California at Berkeley, the University of California at San Francisco, the California Department of Health Services, and the Lawrence Berkeley Laboratory. A total of fourteen projects are proposed. These projects cover a wide range of Superfund- related areas and chemicals, and address the relationship between hazardous substances in the environment and their impact on human health and ecosystem viability. Research is focused upon four areas: 1) the development of biological markers for use in epidemiological studies; 2) variability in human metabolism and pharmacokinetics and its prediction by mathematical modeling; 3) the transport of chemicals off site, into homes and ecosystems; and 4) improved methods for remediation and the destruction of toxic chemicals found at Superfund sites. Four chemicals of high interest to the Superfund program, namely benzene, trichloroethylene, arsenic and lead, are focused on in particular. Projects 12, 3, and 6 will focus on the development of biomarkers of internal dose and genetic damage in humans. New and existing biomarkers will be applied in epidemiological studies of arsenic and benzene exposure (Projects 16 and 4). Projects 15, 9, and 10 will focus on pharmacokinetics and mathematical modeling. The aim of these projects is to provide better methods for the prediction of risk to humans exposed to low levels of toxic contaminants. Projects 18-22 form the engineering and ecological component of the program project. Research in these projects will improve our understanding of the transport of chemicals through the multimedia environment which characterizes Superfund sites, and examine the ability of chemicals to enter homes via the soil gas (Project 21) and impact ecosystems by producing genotoxic effects (Project 20). In addition, new methods for the removal and destruction of toxic chemicals found at hazardous waste sites will be studied. Project 19 will continue to develop methods employing steam injection and vacuum extraction to remove chemicals from hazardous waste sites; Project 10 will investigate the ability of microorganisms to assist in the cleanup of hazardous waste sites and Project 14 will examine the potential hazards associated with the thermal destruction of concentrated wastes, including soil gas. Together these studies should address major issues of concern at Superfund sites through basic research and improve our ability to remediate hazardous waste sites and predict the health effects posed by them.